1. Field of the Invention
The present invention relates to a method and kit for therapeutically treating injuries by inducing acoustic intracellular microstreaming by using low intensity ultrasound. More particularly, the present invention relates to a method and kit which utilizes an ultrasound contrast agent and an ergonomically constructed ultrasonic transducer for placement in proximity to an injury for therapeutically treating the injury by producing acoustic cavitation at the trauma site. The ultrasound contrast agent is introduced into the patient, preferably, the patient's blood stream, prior to emitting ultrasonic waves toward the trauma site to lower the cavitation threshold, i.e., the energy required for cavitation, to a level attainable with low intensity ultrasound.
2. Description of the Related Art
The use of ultrasound or acoustic energy to therapeutically treat and evaluate bone and tissue injuries is known. Impinging ultrasonic pulses having appropriate parameters, e.g., frequency, pulse repetition, and amplitude, for suitable periods of time and at a proper external location adjacent to a bone or tissue injury has been determined to accelerate the natural healing of, for example, bone breaks and fractures.
U.S. Pat. No. 4,530,360 to Duarte describes a basic non-invasive therapeutic technique and apparatus for applying ultrasonic pulses from an operative surface placed on the skin at a location adjacent a bone injury. The applicator described in the Duarte patent has a plastic tube which serves a grip for the operator, an RF plug attached to the plastic tube for connection to an RF source, and internal cabling connected to an ultrasonic transducer. To apply the ultrasound pulses during treatment an operator must manually hold the applicator in place until the treatment is complete. As a result, the patient is, in effect, immobilized during treatment. The longer the treatment period, the more the patient is inconvenienced. The Duarte patent as well as U.S. Pat. No. 5,520,612 to Winder et al. describe ranges of RF signal for creating the ultrasound, ultrasound power density levels, ranges of duration for each ultrasonic pulse, and ranges of ultrasonic pulse frequencies.
U.S. Pat. No. 5,003,965 to Talish et al. relates to an ultrasonic body treatment system having a body-applicator unit connected to a remote control unit by sheathed fiber optic lines. The signal controlling the duration of ultrasonic pulses and the pulse repetition frequency are generated apart from the body-applicator unit. Talish et al. also describes a mounting fixture for attaching the body-applicator unit to a patient so that the operative surface is adjacent the skin location.
It has been demonstrated that the components of acoustic energy that can effect chemical change can be thermal, mechanical (agitational) and cavitational in nature. The largest non-thermal effects are those attributed to stable cavitation and mass transfer. These, in turn, can induce acoustic microstreaming, producing shear stresses on the cellular wall and boundary layer, and in the cytosol. The latter effect, due to intracellular microstreaming, can produce an increase in the metabolic function of the cell.
Since the early sixties, the specific physical and biological mechanisms behind the therapeutic effectiveness of low intensity ultrasound have been extensively investigated. For spatial average-temporal average (SATA) intensities from 0.1–0.5 W/cm2, it is possible to produce the non-thermal, high stress mechanisms of acoustic streaming and cavitation. In vitro tests on isolated fibroblast cells have shown that the effects of ultrasound on the cells are pressure sensitive, suggesting a (stable) cavitation mechanism, caused by the rapid expansion and collapse of microbubbles. The resulting bubble oscillations, possibly including acoustic microstreaming, can generate high shear stress on the cell membrane, which can affect the cell's permeability to sodium and calcium ions. The increase in cell permeability may result in an increase in calcium uptake, an increase in protein and DNA synthesis in fibroblasts, and account for the observed activation of macrophages. The production of fibroblasts and macrophages characterizes the normal fracture repair process.
It has been determined that the cavitation threshold, i.e., the energy required for cavitation, is approximately 0.1 W/cm2 in an aqueous medium and approximately 0.2 W/cm2 in vivo. One in vivo study conducted utilizing a simulated cell membrane attributed the measured ultrasound-induced changes in the properties of cell membranes to changes in diffusion rates produced by fluid layer movement near the membrane. It has also been demonstrated that the value of micromechanical stimuli (0.5 Hz for 17 minutes, daily) significantly improves the healing of tibial fractures. One study was able to correlate this accelerated healing process with the promotion of fracture revascularization. However, for SATA intensities below 0.1 W/cm2, stable cavitation and acoustic micro-streaming seem quite unlikely. In another study, exposure to low intensity ultrasound produced increased levels of aggrecan mRNA in a rat femur model in the early stages of treatment.
In vivo test results indicate that a low SATA intensity from 30–50 mW/cm2 is highly effective in stimulating bone fracture repair. These results support the thesis that ultrasonically-induced mechanical vibrations tend to increase the permeability of the cell membrane.
In other clinical studies, preliminary results indicate that angiogenesis, the development of new blood vessels, is a key component in the initial phase in the cascade of events involved in the bone fracture healing process. The increased vascularity and the micromechanical fluid pressure appear to produce an increase in cellular calcium uptake, resulting in increased protein synthesis, thereby accelerating bone fracture healing and tissue repair.
Accordingly, there is a need for a method and kit for accelerating bone and tissue healing utilizing the scientific and anatomical observations and studies discussed above. That is, there is a need for a method and kit for accelerating bone and tissue healing by lowering the cavitation threshold to a level attainable with low intensity ultrasound to produce acoustic intracellular microstreaming. Since intracellular microstreaming can produce an increase in the metabolic functions, the method and kit would accelerate the healing process.